Our research has demonstrated selective S sensitivity loss very early in diabetes and prior to irreversible complications in the eye (pre- retinopathy). The loss is selective for signals in the S cone pathways and, at least in early stages involves neither other color pathways nor the achromatic processing of signals. The deficit is revealed under bright yellow field adaptation conditions and our experiments suggest the involvement of some anomaly of the sensitivity control mechanisms beyond the receptor. (Proposed tests will identify extent of loss under conditions of neutral adaptation using spatio-chromatic modulations on computer generated video displays). The S sensitivity loss is not only associated with the more advanced retinopathic sign of edema but, we have shown on a limited study population that it closely follows the blood glucose levels of diabetics over minutes, hours or months. Our finding of direct metabolic effects on S sensitivity, as opposed to a loss associated with vascular complication of the breakdown of the blood-retina barrier, is central to a series of proposed experiments on diabetics with early and different levels of diabetic eye complications and diabetic control. The hypothesis of the existence of a critical period of reversibility of function, prior to retinopathy development is specifically explored. Related experiments will utilize both objective and psychophysical approaches to isolate the site of early diabetic complications at the molecular level in the function of RPE, the S cone receptor level with new ERG approaches to recording S cone responses, the post-receptoral inner nuclear retinal level with B-wave responses to S pathway stimulation, and chromatic pathway selectivity recorded at the striate cortex level with VEP measures. All measures are applications of instrumentation and techniques developed within the last grant period. The overall goal is to identify the earliest functional vision changes associated with the complications of diabetes that can provide insight as to the site of action of the diabetes, the prognostic indicators of impending irreversible damage to the visual system and potent indicators of the appropriate choice of treatment, and a measure of treatment efficacy for diabetic complications.